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Reversed Immunoglycomics Identifies α-Galactosyl-Bearing Glycotopes Specific for Leishmania major Infection

Montoya, Alba L., Austin, Victoria, Portillo, Susana, Vinales, Irodiel, Ashmus, Roger A., Estevao, Igor, Jankuru, Sohan R., Alraey, Yasser, Al-Salem, Waleed, Acosta-Serrano, Alvaro ORCID:, Almeida, Igor C. and Michael, Katja (2021) 'Reversed Immunoglycomics Identifies α-Galactosyl-Bearing Glycotopes Specific for Leishmania major Infection'. JACS Au, Vol 1, Issue 8, pp. 1275-1287.

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All healthy humans have high levels of natural anti-α-galactosyl (α-Gal) antibodies (elicited by yet uncharacterized glycotopes), which may play important roles in immunoglycomics: (a) potential protection against certain parasitic and viral zoonotic infections; (b) targeting of α-Gal-engineered cancer cells; (c) aiding in tissue repair; and (d) serving as adjuvants in α-Gal-based vaccines. Patients with certain protozoan infections have specific anti-α-Gal antibodies, elicited against parasite-derived α-Gal-bearing glycotopes. These glycotopes, however, remain elusive except for the well-characterized glycotope Galα1,3Galβ1,4GlcNAcα, expressed by Trypanosoma cruzi. The discovery of new parasitic glycotopes is greatly hindered by the enormous structural diversity of cell-surface glycans and the technical challenges of classical immunoglycomics, a top-down approach from cultivated parasites to isolated glycans. Here, we demonstrate that reversed immunoglycomics, a bottom-up approach, can identify parasite species-specific α-Gal-bearing glycotopes by probing synthetic oligosaccharides on neoglycoproteins. This method was tested here seeking to identify as-yet unknown glycotopes specific for Leishmania major, the causative agent of Old-World cutaneous leishmaniasis (OWCL). Neoglycoproteins decorated with synthetic α-Gal-containing oligosaccharides derived from L. major glycoinositolphospholipids served as antigens in a chemiluminescent enzyme-linked immunosorbent assay using sera from OWCL patients and noninfected individuals. Receiver-operating characteristic analysis identified Galpα1,3Galfβ and Galpα1,3Galfβ1,3Manpα glycotopes as diagnostic biomarkers for L. major-caused OWCL, which can distinguish with 100% specificity from heterologous diseases and L. tropica-caused OWCL. These glycotopes could prove useful in the development of rapid α-Gal-based diagnostics and vaccines for OWCL. Furthermore, this method could help unravel cryptic α-Gal-glycotopes of other protozoan parasites and enterobacteria that elicit the natural human anti-α-Gal antibodies.

Item Type: Article
Subjects: QW Microbiology and Immunology > Immunity by Type > QW 541 Natural immunity. Immunogenetics
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 715 Visceral leishmaniasis
WR Dermatology > Parasitic Skin Diseases > WR 350 Tropical diseases of the skin. Mucocutaneous leishmaniasis. Leishmaniasis
Faculty: Department: Biological Sciences > Vector Biology Department
Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):
Depositing User: Samantha Sheldrake
Date Deposited: 02 Sep 2021 14:57
Last Modified: 17 Aug 2022 08:59


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